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Abstract Background Premature rupture of the membranes (PROM) is a key cause of preterm birth and represents a major cause of neonatal mortality and morbidity. Natural products N-acetyl-d-galactosamine (GalNAc), which are basic building blocks of important polysaccharides in biological cells or tissues, such as chitin, glycoproteins, and glycolipids, may improve possible effects of wound healing. Methods An in vitro inflammation and oxidative stress model was constructed using tumor necrosis-α (TNF-α) and lipopolysaccharide (LPS) action on WISH cells. Human amniotic epithelial cells (hAECs) were primarily cultured by digestion to construct a wound model. The effects of GalNAc on anti-inflammatory and anti-oxidative stress, migration and proliferation, epithelial-mesenchymal transition (EMT), glycosaminoglycan (GAG)/hyaluronic acid (HA) production, and protein kinase B (Akt) pathway in hAECs and WISH cells were analyzed using the DCFH-DA fluorescent probe, ELISA, CCK-8, scratch, transwell migration, and western blot to determine the mechanism by which GalNAc promotes amniotic wound healing. Results GalNAc decreased IL-6 expression in TNF-α-stimulated WISH cells and ROS expression in LPS-stimulated WISH cells (P 0.05). GalNAc upregulated the expression of sGAG in WISH cells (P 0.05). Conclusions GalNAc might be a potential target for the prevention and treatment of PROM through the galectin pathway, including (i) inflammation; (ii) epithelial-mesenchymal transition; (iii) proliferation and migration; and (iv) regression, remodeling, and healing.

BackgroundAtopic eczema (AE) is a common atopic inflammatory skin disease affecting 2.1–4.9% of the population in different countries. Pruritus, one of the most burdensome symptoms, is often underestimated for the problems it can cause, creating a vicious loop of itching, scratching, and lichenification. Therefore, further research into practical and safe treatments that relieve itchy symptoms and enhance skin protection is key to overcoming AE. Acupuncture, with or without electrical stimulation, is one of the most commonly used therapeutic measures to treat AE. This trial aimed to objectively evaluate the efficacy and safety of the electroacupuncture (EA) antipruritic technique in AE pruritus and obtain high-level clinical evidence for the popularization and application of EA for AE.Methods and analysisThis multicenter, single-blinded, randomized controlled trial is planned to transpire from April 15, 2023, to June 30, 2025. We will recruit 132 participants with AE (44 per group). Participants will be assigned randomly to three equal-sized groups: EA, sham electroacupuncture, and sham acupuncture. Treatment will be administered three times a week during the 2-week intervention phase. The primary outcome measure is the Visual Analog Scale, with a numeric rating scale to evaluate pruritus. Secondary outcome measures include the Eczema Area and Severity Index and Dermatology Life Quality Index. Other outcome measures include physical examination, serum IgE, and safety evaluation. The number, nature, and severity of adverse events will be carefully recorded.Trial registrationClinicalTrials.gov, 22Y11922200. Registered 3 September 2022, https://register.clinicaltrials.gov.

Aromatic ketones are important pharmaceutical intermediates, especially the pyridin-2-yl-methanone motifs. Thus, synthetic methods for these compounds have gained extensive attention in the last few years. Transition metals catalyze the oxidation of Csp3-H for the synthesis of aromatic ketones, which is arresting. Here, we describe an efficient copper-catalyzed synthesis of pyridin-2-yl-methanones from pyridin-2-yl-methanes through a direct Csp3-H oxidation approach with water under mild conditions. Pyridin-2-yl-methanes with aromatic rings, such as substituted benzene, thiophene, thiazole, pyridine, and triazine, undergo the reaction well to obtain the corresponding products in moderate to good yields. Several controlled experiments are operated for the mechanism exploration, indicating that water participates in the oxidation process, and it is the single oxygen source in this transformation. The current work provides new insights for water-involving oxidation reactions.

The southern part of the Kyushu-Palau Ridge (KPR) is located at the conjunction of the West Philippine Basin, the Parece Vela Basin, the Palau Basin, and the Caroline Basin. This area has extremely complex structures and is critical for the research on the tectonic evolution of marginal seas in the Western Pacific Ocean. However, only few studies have been completed on the southern part, and the geophysical fields and deep structures in this part are not well understood. Given this, this study finely depicts the characteristics of the gravity and magnetic anomalies and extracts information on deep structures in the southern part of the KPR based on the gravity and magnetic data obtained from the 11th expedition of the deep-sea geological survey of the Western Pacific Ocean conducted by the Guangzhou Marine Geological Survey, China Geological Survey using the R/V Haiyangdizhi 6. Furthermore, with the data collected on the water depth, sediment thickness, and multichannel seismic transects as constraints, a 3D density model and Moho depths of the study area were obtained using 3D density inversion. The results are as follows. (1) The gravity and magnetic anomalies in the study area show distinct zoning and segmentation. In detail, the gravity and magnetic anomalies to the south of 11°N of the KPR transition from high-amplitude continuous linear positive anomalies into low-amplitude intermittent linear positive anomalies. In contrast, the gravity and magnetic anomalies to the north of 11°N of the KPR are discontinuous and show alternating positive and negative anomalies. These anomalies can be divided into four sections, of which the separation points correspond well to the locations of deep faults, thus, revealing different field-source attributes and tectonic genesis of the KPR. (2) The Moho depth in the basins in the study area is 6–12 km. The Moho depth in the southern part of KPR show segmentation. Specifically, the depth is 10–12 km to the north of 11°N, 12–14 km from 9.5°N to 11°N, 14–16 km from 8.5°N to 9.5°N, and 16–25 km in the Palau Islands. (3) The KPR is a remnant intra-oceanic arc with the oceanic-crust basement.which shows noticeably discontinuous from north to south in geological structure and is intersected by NEE-trending lithospheric-scale deep faults. With large and deep faults F3 and F1 (the Mindanao fault) as boundaries overall, the southern part of the KPR can be divided into three zones. In detail, the portion to the south of 8.5°N (F3) is a tectonically active zone, the KPR portion between 8.5°N and 11°N is a tectonically active transition zone, and the portion to the north of 11°N is a tectonically inactive zone. (4) The oceanic crust in the KPR is slightly thicker than that in the basins on both sides of the ridge, and it is inferred that the KPR formed from the thickening of the oceanic crust induced by the upwelling of deep magma in the process of rifting of remnant arcs during the Middle Oligocene. In addition, it is inferred that the thick oceanic crust under the Palau Islands is related to the constant upwelling of deep magma induced by the continuous northwestward subduction of the Caroline Plate toward the Palau Trench since the Late Oligocene. This study provides a scientific basis for systematically understanding the crustal attributes, deep structures, and evolution of the KPR.©2021 China Geology Editorial Office.

Abstract AgNPs are nanomaterials with many potential biomedical applications. In this study, the two novel yeast strains HX-YS and LPP-12Y capable of producing biological silver nanoparticles were isolated. Sequencing of ribosomal DNA-ITS fragments, as well as partial D1/D2 regions of 26S rDNA indicated that the strains are related to species from the genus Metschnikowia. The BioAgNPs produced by HX-YS and LPP-12Y at pH 5.0–6.0 and 26 °C ranged in size from 50 to 500 nm. The antibacterial activities of yeast BioAgNPs against five pathogenic bacteria were determined. The highest antibacterial effect was observed on P. aeruginosa, with additional obvious effects on E. coli ATCC8099 and S. aureus ATCC10231. Additionally, the BioAgNPs showed antiproliferative effects on lung cancer cell lines H1975 and A579, with low toxicity in Beas 2B normal lung cells. Therefore, the AgNPs biosynthesized by HX-YS and LPP-12Y may have potential applications in the treatment of bacterial infections and cancer.

Abstract Background Acute kidney injury (AKI) is the main life-threatening complication of crush syndrome (CS), and myoglobin is accepted as the main pathogenic factor. The pattern recognition receptor retinoicacid-inducible gene I (RIG-I) has been reported to exert anti-viral effects function in the innate immune response. However, it is not clear whether RIG-I plays a role in CS-AKI. The present research was carried out to explore the role of RIG-I in CS-AKI. Methods Sprague-Dawley rats were randomly divided into two groups: the sham and CS groups (n = 12). After administration of anesthesia, the double hind limbs of rats in the CS group were put under a pressure of 3 kg for 16 h to mimic crush conditions. The rats in both groups were denied access to food and water. Rats were sacrificed at 12 h or 36 h after pressure was relieved. The successful establishment of the CS-AKI model was confirmed by serum biochemical analysis and renal histological examination. In addition, RNA sequencing was performed on rat kidney tissue to identify molecular pathways involved in CS-AKI. Furthermore, NRK-52E cells were treated with 200 μmol/L ferrous myoglobin to mimic CS-AKI at the cellular level. The cells and cell supernatant samples were collected at 6 h or 24 h. Small interfering RNAs (siRNA) was used to knock down RIG-I expression. The relative expression levels of molecules involved in the RIG-I pathway in rat kidney or cells samples were measured by quantitative Real-time PCR (qPCR), Western blotting analysis, and immunohistochemistry (IHC) staining. Tumor necrosis factor-α (TNF-α) was detected by ELISA. Co-Immunoprecipitation (Co-IP) assays were used to detect the interaction between RIG-I and myoglobin. Results RNA sequencing of CS-AKI rat kidney tissue revealed that the different expression of RIG-I signaling pathway. qPCR, Western blotting, and IHC assays showed that RIG-I, nuclear factor kappa-B (NF-κB) P65, p-P65, and the apoptotic marker caspase-3 and cleaved caspase-3 were up-regulated in the CS group (P

BackgroundBiological agents have been used with extreme caution in children because of their possible adverse effects.ObjectivesThis study used high-quality randomized controlled trials (RCTs) to provide high-level evidence to assess the effectiveness and safety of biological agents for treating children with psoriasis.MethodsWe searched PubMed, Embase, Cochrane, and Web of Science databases through October 31, 2021. We included trials reporting at least one adverse event after treatment with biological agents of patients less than 18-year-old diagnosed with psoriasis. RevMan 5.3 and Stata 15.0 software were used for meta and Bayesian analyses.ResultsSix trials with 864 participants were included in the analysis. The results showed a 2.37-fold higher response rate in all biologics groups than in the control group for psoriasis area and severity index 75 (PASI75) (RR= 2.37, P-value < 0.01, 95% confidence interval [CI] [1.22, 4.62]). Compared with placebo, the PASI75 response rates of etanercept (RR= 2.82, 95% [CI] [1.10, 7.21]), ustekinumab low dose (RR= 7.45, 95%[CI] [1.25, 44.58]), and ustekinumab high dose (RR= 7.25, 95%[CI] [1.21, 43.41]) were superior. Additionally, the incidence of total adverse reactions was 1.05 times higher for biologics than for controls, indicating a good safety profile (RR= 1.05, P-value = 0.53, 95%[CI] [0.92, 1.19]). Overall, these six high-quality randomized controlled trials suggest that biologics are effective and safe for pediatric patients with psoriasis.LimitationsInclusion of few relevant, high-quality RCTs.ConclusionThe results of this study indicate that biologics can be used to treat children with moderate-to-severe psoriasis without the risk of adverse effects. Ustekinumab showed the best efficacy and the fewest adverse effects.

The fetal membranes healing is a complex and dynamic process of replacing devitalized and missing cellular structures and tissue layers. Multiple cells and extracellular matrices, and cell differentiation, migration and proliferation may participate in restoring the integrity of damaged tissue, however this process still remains unclear. Therefore, there is a need to identify and integrate new ideas and methods to design a more effective dressing to accelerate fetal membrane healing. This review explores the function and role of galectins in the inflammatory, epithelial mesenchymal transition, proliferative migration, and remodeling phases of fetal membrane healing. In conclusion, the preliminary findings are promising. Research on amnion regeneration is expected to provide insight into potential treatment strategies for premature rupture of membranes.

Background: Traditional Chinese medicine is effective in the treatment of psoriasis and can significantly reduce skin inflammation and psoriatic lesions with minimal side effects. Shikonin (SHI) and β,β-dimethylacryloyl alkannin (DMA), the main active components of Lithospermum erythrorhizon, have strong anti-inflammatory effects. This systematic review aimed to evaluate the efficacy and safety of Lithospermum erythrorhizon and its main active components and to elucidate the potential mechanisms of their action in psoriasis treatment.Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Scientific Journals, Wan Fang, and Chinese Biomedicine databases were systematically searched for articles published between 1 January 1970, and 31 February 2021. We included clinical and preclinical studies that examined the effects of Lithospermum erythrorhizon and its active components on psoriasis. All data were analyzed using RevMan 5.3 software. The Cochrane and SYRCLE’s risk-of-bias tools were used to assess the quality of all studies.Results: Eleven clinical trials including 1024 participants and 23 preclinical studies were assessed. Meta-analysis showed that when treating patients with psoriasis, the Chinese herbal medicine (CHM) formulas with Lithospermum erythrorhizon as the sovereign herb can significantly improve psoriatic dermatitis, which can significantly reduce the psoriasis area and severity index (PASI) score (mean difference [MD] = -2.00, 95% confidence interval [CI] [-3.19, -0.80], p = 0.001; I2 = 85%). The incidence rates of diarrhea (risk ratio = 0.21, 95% CI [0.06, 0.81], p = 0.02) were higher in the CHM formulas group than in the control group, whereas other adverse events were not significantly different between the two groups (p > 0.05). We evaluated the PASI score of mice on day 7 and found that SHI and DMA also alleviated psoriatic lesions (MD = -3.36, 95% CI [-4.67, -2.05], p < 0.00001, I2 = 94%). Furthermore, the epidermal thickness decreased more after SHI or DMA treatment than in the control group (MD = -34.42, 95%CI [-41.25, -27.59], p < 0.00001, I2 = 93%). Based on preclinical studies, we also summarized and mapped the mechanisms of SHI and DMA in the treatment of psoriasis.Conclusion: Available findings demonstrated that Lithospermum erythrorhizon combined with other conventional treatments is useful in treating psoriasis. Preclinical evidence has shown that the active components of Lithospermum erythrorhizon exhibit a potential anti-inflammatory effect, promote keratinocyte apoptosis, inhibit keratinocyte proliferation and angiogenesis, and block the cell cycle. In summary, our findings suggest that Lithospermum erythrorhizon and its active components can be used to treat psoriasis.

Lifetime requirements and coverage demands are emphasized in wireless sensor networks. An area coverage algorithm based on differential evolution is developed in this study to obtain a given coverage ratio ε . The proposed algorithm maximizes the lifetime of wireless sensor networks to monitor the area of interest. To this end, we translate continuous area coverage into classical discrete point coverage, so that the optimization process can be realized by wireless sensor networks. Based on maintaining the ε -coverage performance, area coverage algorithm based on differential evolution takes the minimal energy as optimization objective. In area coverage algorithm based on differential evolution, binary differential evolution is redeveloped to search for an improved node subset and thus meet the coverage demand. Taking into account that the results of binary differential evolution are depended on the initial value, the resulting individual is not an absolutely perfect node subset. A compensation strategy is provided to avoid unbalanced energy consumption for the obtained node subset by introducing the positive and negative utility ratios. Under the helps of those ratios and compensation strategy, the resulting node subset can be added additional nodes to remedy insufficient coverage, and redundancy active nodes can be pushed into sleep state. Furthermore, balance and residual energy are considered in area coverage algorithm based on differential evolution, which can expand the scope of population exploration and accelerate convergence. Experimental results show that area coverage algorithm based on differential evolution possesses high energy and computation efficiencies and provides 90% network coverage.

Background: Biological agents have been used with extreme caution in children because of their possible adverse effects. Objectives: This study used high-quality randomized controlled trials (RCTs) to provide high-level evidence to assess the effectiveness and safety of biological agents for treating children with psoriasis. Methods: We searched PubMed, Embase, Cochrane, and Web of Science databases through October 31, 2021. We included trials reporting at least one adverse event after treatment with biological agents of patients less than 18-year-old diagnosed with psoriasis. RevMan 5.3 and Stata 15.0 software were used for meta and Bayesian analyses. Results: Six trials with 864 participants were included in the analysis. The results showed a 2.37-fold higher response rate in all biologics groups than in the control group for psoriasis area and severity index 75 (PASI75) (RR= 2.37, Pvalue < 0.01, 95% confidence interval [CI] [1.22, 4.62]). Compared with placebo, the PASI75 response rates of etanercept (RR= 2.82, 95% [CI] [1.10, 7.21]), ustekinumab low dose (RR= 7.45, 95%[CI] [1.25, 44.58]), and ustekinumab high dose (RR= 7.25, 95%[CI] [1.21, 43.41]) were superior. Additionally, the incidence of total adverse reactions was 1.05 times higher for biologics than for controls, indicating a good safety profile (RR= 1.05, P-value = 0.53, 95%[CI] [0.92, 1.19]). Overall, these six high-quality randomized controlled trials suggest that biologics are effective and safe for pediatric patients with psoriasis. Limitations: Inclusion of few relevant, high-quality RCTs. Conclusion: The results of this study indicate that biologics can be used to treat children with moderate-to-severe psoriasis without the risk of adverse effects. Ustekinumab showed the best efficacy and the fewest adverse effects. [ABSTRACT FROM AUTHOR]

Studies on the interaction of the active constituents after Strychni Semen combined with Paeoniae Radix Alba. Following transdermal administration to mouse, the content alterations in paeoniflorin after application of a combination of Strychni Semen extract (SSE) and Paeoniae Radix Alba extract (PRAE) by in vitro skin permeation were observed. The penetration quantity, infiltration rate and skin retention quantity of paeoniflorin in co-administrated with SSE were increased significantly (P<0.05). In the skin and brain, the peak concentration (Cmax) and the area under the concentration-time curve (AUC0→t) of brucine and strychnine in co-administrated with PRAE were decreased significantly (P<0.05), and the Cmax and AUC0→t of paeoniflorin in co-administrated with SSE increased significantly (P<0.05). These results showed that the co-administrated of SSE and PRAE can play an attenuation and synergistic effect [ABSTRACT FROM AUTHOR]

We have identified a robust grassy-edge localized mode (ELM) operation regime for future tokamak reactors. The regime exists within a pedestal top electron collisionality (ν*) window at high global poloidal beta (βp). The existence of an upper ν* limit for grassy-ELMs is consistent with results previously reported in experiments (Oyama et al 2010 Nucl. Fusion50 064014), while the existence of a lower ν* limit has not been reported previously. Using EPED and BOUT  +  +, a theoretical model that quantitatively explains the physics of the grassy-ELMs within the window, which distinguishes them from the small mixed-ELMs at lower ν*, is presented for the first time. A peeling-ballooning stability boundary is obtained by scanning the operating density space. The change in density corresponds to a change in ν* that affects the pedestal bootstrap current. High βp leads to a strong Shafranov shift, which affects the flux surface averaged pressure drive. The two effects combine to create a peeling-dominated window in intermediate ν* buffered by ballooning-dominated regimes. Only the peeling-dominated regime shows a cyclic behavior in the perturbed pressure during the nonlinear simulation of an ELM crash, reminiscent of grassy-ELM dynamics. Similarly, the energy released across the separatrix is demonstrated to be significantly smaller. The quick recovery of the ELM crash is explainable by the rapid rise of a low n kink-peeling instability when the pedestal current Iped exceeds a threshold at high βp. It minimizes the excursion beyond marginal stability and is absent in the ballooning-dominated regime. Comparison with recent experiments over a range of βp and ν* strongly supports the physical picture proposed by the modeling. [ABSTRACT FROM AUTHOR]

Investigation on the equilibrium operation regime, its ideal magnetohydrodynamics (MHD) stability and edge localized modes (ELM) characteristics is performed for the China Fusion Engineering Test Reactor (CFETR). The CFETR operation regime study starts with a baseline scenario (R  =  5.7 m, BT  =  5 T) derived from multi-code integrated modeling, with key parameters varied to build a systematic database. These parameters, under profile and pedestal constraints, provide the foundation for the engineering design. The long wavelength low-n global ideal MHD stability of the CFETR baseline scenario, including the wall stabilization effect, is evaluated by GATO. It is found that the low-n core modes are stable with a wall at r/a  =  1.2. An investigation of intermediate wavelength ideal MHD modes (peeling ballooning modes) is also carried out by multi-code benchmarking, including GATO, ELITE, BOUT++ and NIMROD. A good agreement is achieved in predicting edge-localized instabilities. Nonlinear behavior of ELMs for the baseline scenario is simulated using BOUT++. A mix of grassy and type I ELMs is identified. When the size and magnetic field of CFETR are increased (R  =  6.6 m, BT  =  6 T), collisionality correspondingly increases and the instability is expected to shift to grassy ELMs. [ABSTRACT FROM AUTHOR]